Frequency adjustment in high intensity focused ultrasound treatment apparatus

ABSTRACT

The invention concerns an apparatus for treating a biological sample by emitting focused high intensity ultrasounds towards a focal point, characterised in that it comprises means emitting wideband focused ultrasounds. The apparatus enables to adjust the focused ultrasound frequency according to the target attenuation, the thickness of the tissues traversed, the temperature evolution, or the lesion displacement during emission.

BACKGROUND OF THE INVENTION

This invention relates to apparatus for treating a biological target bydelivering focused ultrasound at high intensity to a focal point. Itfurther relates to a method for adjusting the frequency of apparatus fortreating a biological target by delivering high intensity focusedultrasound to a focal point.

The invention falls in the field of tissue treatment using focusedultrasound, and more particularly the field of tissue destruction insidean organism by creation of high temperatures using focused ultrasound.

In the general field of focused ultrasound, as the person skilled in theart knows, various types of treatment can be distinguished: thetreatment that has been around longest is treatment by lithotripsy,which applies to destroying hard bodies; this type of treatment usesshock waves, i.e. short high power pulses. Later, it was proposed totreat soft issue by hyperthermia, by heating tissue to slightly elevatedtemperatures, i.e. less than 45° C. Hyperthermia involves emittingultrasound in the form of long and lower power pulses to the tissue tobe treated. Finally, currently, treatment of soft tissue using highintensity focused ultrasound, generally called HIFU (high intensityfocused ultrasound) is being proposed. HIFU treatment involves heatingtissue to elevated temperatures, typically greater than 45° C.

These various types of treatment involve very different technicalproblems, both as regards sending and focusing of the ultrasound as wellas its propagation.

HIFU treatment raises different problems. Generally speaking, the aim isto improve effectiveness of treatment, i.e. destruction of selectedtissue. For this, the first problem resides in a suitable choice of theultrasound transmission parameters; the latter, and in particularultrasound frequency, need to be chosen very accurately. They generallydepend on numerous factors such as: target depth, nature of tissue, typeof necrosis desired.

A second problem is that of gaining access to the targets or tissue tobe treated. Due to patient anatomy, targets are sometimes difficult toget at for ultrasound beams. Moving the transducer has been proposed;moving the transducer may however also be limited by patient morphology.In prostate treatment by endorectal probe, various solutions to thisproblem have been proposed, see for example French Patent applicationsserial numbers 9102620, 9309158, 9608096, 9401304, 9406539. Thesevarious solutions could still be improved, for ensuring bettertreatment, in precise areas, by hyperthermia or HIFU.

A third problem resides in the fact that the beam emitted by anultrasound focused transducer is generally effective within a fixedregion, called the focal zone. Now, this focal zone most frequently issmaller than the size of the target tissue. Treatment of extensivetargets is consequently a problem. One proposition was to successivelyemploy, by endorectal route, transducers of various focal lengths, forexample, in the case of the prostate, a first one, of short focallength, suitable for treating the posterior region and another one, oflonger focal length, for the anterior region. This method involveschanging the probe during the session, which is not desirable.

One proposed solution to this third problem consisted in employingvariable focal length transducers. These can be constructed from anarray of individual transducers. Do-Huu was the first to employ annulararrays for hyperthermia ((JP Do-Huu, P Hartmann, Annular arraytransducer for deep acoustic hyperthermia, IEEE Ultrasonics Symp, Vol81CH1689-9, pp. 705-710, 1981, or U.S. Pat. No. 4,586,512 of May, 1986).Still for hyperthermia, we can cite the work of Cain (C A Cain, S AUmemura, Concentric-ring and sector vortex phased array applicators forultrasound hyperthermia therapy, IEEE Trans Microwave Theory Tech, volMTT-34, pp 542-551, 1986) and the work of Ebbini (E S Ebbini, C A Cain,A spherical-section ultrasound phased array applicator for deeplocalized hyperthermia, IEEE Trans Biomed Eng, vol 38, pp 634-643,1991).

J Y Chapelon et al, The feasibility of tissue ablation using highintensity electronically focused ultrasound, IEEE Ultrasonics Symp, Vol93CH3301-9, pp 1211-1214, 1993 proposed using annular phased arrays forHIFU.

The work of Hynynen and corresponding publications, for example KHynynen et al, Feasibility of using ultrasound phased rays for MRImonitored noninvasive surgery, IEEE Trans UFFC, Vol 43, No. 6, 1996proposes HIFU treatments.

A variable focal length transducer can also be constructed using a fixedfocus transducer and an acoustic lens, as disclosed in French patent2,715,822 in the name of Dory.

In every case, it is essential to adapt treatment parameters to targetdepth for obtaining satisfactory therapeutic effect. In particular, theoperating frequency of the transducer must be determined. This iscalculated from the equation giving absorbed acoustic power per unit ofvolume (W/cm³) at the focus of a focused transducer:

Q=2αFI ₀ Ge ^(−2αFd)  (1)

where:

Q is the acoustic power absorbed per unit of volume

α is the acoustic attenuation factor (Neper/cm/MHz)

I₀ is the acoustic intensity at the transducer emission surface (W/cm²)

G is antenna gain

F is frequency (MHz)

d is the thickness of the absorbing medium (cm) as explained in Hill C.R. Optimum acoustic frequency for focused ultrasound surgery inUltrasound in Med & Biol; 20; 271-277; 1994 and Lesion development infocused ultrasound surgery: a general model in Ultrasound in Med & Biol;20; 259-269; 1994.

This formal approach is known and employed by designers of apparatus fortissue treatment by focused ultrasound, for determining optimumoperating frequency of a therapy transducer depending on depth oracoustic attenuation of the intended target. This choice is defined apriori and remains fixed for a given transducer.

Seppi, in U.S. Pat. No. 4,875,487 discloses, for hyperthermia, use ofwideband transducers and choice of working frequency range depending ontarget depth. That Patent additionally proposes employing a widebandsignal so as to create incoherent beams which are, consequently,unfocused.

European patent application 0,351,610 discloses wideband transducersfocused electronically, focusing being controlled as a function ofcavitation.

SUMMARY OF THE INVENTION

This invention proposes an elegant and simple solution to the problem ofdistributing acoustic power in ultrasound treatment; it ensures bettercontrol of overall power, and good definition of the region treated.

More precisely, the invention provides apparatus for treating abiological target by emitting high power focused ultrasound towards afocal point, comprising wideband transducer means for emittingultrasound, means for controlling said transducer means for emittingfocused ultrasound over a narrow frequency range, and means foradjusting the frequency range of said controlling means as a function ofmeasurement results.

According to one embodiment of the apparatus, the means for emittingultrasound have a variable focal length.

According to a further embodiment, the apparatus additionally comprisescoupling means of variable thickness adjacent to said ultrasoundemitting means.

The ultrasound emitting means preferably have a fixed focal length andthe apparatus can additionally comprise variable thickness couplingmeans adjacent to the emitting means.

According to one embodiment, the apparatus additionally comprises meansfor measuring acoustic attenuation in the region of a focal point, themeans for adjusting frequency range performing adjustment of the focusedultrasound frequency range as a function of results supplied by acousticattenuation measurement means.

The apparatus preferably comprises means for measuring mean acousticattenuation variation close to a focal point, and the means foradjusting frequency range performing adjustment of a focused ultrasoundfrequency range as a function of results supplied by the means formeasuring mean acoustic attenuation variation.

According to one embodiment, the apparatus additionally comprises meansfor calculating or measuring temperature in the region of a focal point,and the means for adjusting frequency range perform adjustment of thefocused ultrasound frequency range as a function of results supplied bysaid means for calculating or measuring temperature.

According to a further embodiment, the apparatus comprises means fordetermining the thickness of. tissue through which ultrasound haspassed, and the means for adjusting frequency range perform adjustmentof the focused ultrasound frequency range as a function of resultssupplied by said thickness-determining means.

The means for determining a thickness of tissue through which ultrasoundhas passed preferably comprises means for measuring thickness ofvariable-thickness coupling means.

According to one embodiment, the apparatus comprises means forcalculating a displacement of a lesion as a function of time ofshooting, and for calculating thickness through which ultrasound haspassed, the adjustment means performing focused ultrasound frequencyadjustment as a function of of displacement and thickness.

According to a further embodiment, the apparatus comprises means forcalculating lesion depth as a function of shooting time, the adjustmentmeans performing adjustment of focused ultrasound frequency as afunction of depth.

In one embodiment, the adjustment means perform adjustment of frequencyrange before a shot.

In a further embodiment, the adjustment means perform frequency rangeadjustment during a shot.

A method for adjusting the frequency of apparatus for treating abiological target by emitting high intensity focused ultrasound towardsa focal point is provided, the method comprising the steps of:

measuring attenuation or variation in attenuation of a biologicaltarget; and

adjusting focused ultrasound frequency as a function of measuredattenuation.

A method for adjusting the frequency of apparatus for treating abiological target by emitting high intensity focused ultrasound towardsa focal point is also provided comprising the steps of:

measuring a thickness of tissue through which ultrasound has passed; and

adjusting focused ultrasound frequency as a function of this thickness.

Measurement of tissue thickness through which ultrasound has passed cancomprise the steps of:

calculating a focal length between an ultrasound sender and a focalpoint;

measuring the distance between the sender and a first interface with abody containing the target; and

subtracting a distance between the sender and the first interface fromfocal length in order to obtain a thickness of tissue through whichultrasound has passed.

Ultrasound frequency adjustment is preferably performed so as to apply agiven power Q to a target.

Ultrasound frequency adjustment is advantageously performed byapplication of the following formula:

Q=2αFI ₀Ge^(−2αFd)  (1)

where:

Q is the acoustic power absorbed per unit of volume

α is the acoustic attenuation factor (Neper/cm/MHz)

I₀ is the acoustic intensity at the transducer emission surface (W/cm²)

G is antenna gain

F is frequency (MHz)

d is the thickness of the absorbing medium (cm).

In one embodiment of the method, the step of frequency adjustment isperformed before a shot.

In another embodiment, the step of frequency adjustment is performedduring a shot.

Further characteristics and advantages of the invention will becomeclear from the description which follows of some embodiments, providedby way of example and with reference to the attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatical view of HIFU apparatus for carrying out theinvention.

FIG. 2 is a flow chart of one possible procedure for frequencyadjustment according to the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The invention proposes, in HIFU apparatus, to make the ultrasoundfrequency used vary as a function of the measured acoustic attenuationof the target, or of variations in the measured attenuation. It alsoproposes employing wideband ultrasound emitting means, for emittingultrasound in a narrow frequency band, this frequency band varying as afunction of the measured attenuation or attenuation variation.

The invention goes against the teaching of prior art documents whichdisclose the use of wideband transducers. In these documents, widebandtransducers are employed for emitting ultrasound over a wide frequencyrange and hot for emitting ultrasound over a narrow frequency band.

For the person skilled in the art, or the specialist in focusedultrasound, the term “wideband” covers around 50% of the centralfrequency, equivalent for example to 2-3 MHz. The frequencies habituallyemployed in therapy by hyperthermia or HIFU are in general comprisedbetween 1 MHz and 5 MHz.

Inversely, the term “narrowband” signifies, for the person skilled inthe art, a reduced frequency range with respect to the centralfrequency; “single frequency” means a range of frequencies as reduced aspossible, taking account of technical constraints on the emittingequipment; ultrasound emission for therapeutic purposes is generallyconsidered as single frequency when the range of frequencies transmittedis less than about 5% of the ultrasound central frequency.

The invention also proposes a solution to the new problem of variationin attenuation as a function of the target and of individual patients.It is based upon the surprising finding that acoustic attenuation variesfrom one patient to another, even for the same tissue. On a sample aslimited as 30 persons, measurements performed on the prostate show thatacoustic attenuation varies from one patient to the next in a ratio ofaround 50%. This introduces a fresh problem of the deterioration inreproduceability of treatment, and which is incompatible with goodtreatment effectiveness.

The invention also goes against a fairly widespread prejudice in theprior art: in all the documents discussing HIFU, the calculations makereference to a fixed value for tissue attenuation. This value generallyis taken from publications. It is consequently generally accepted that agiven tissue will have a fixed acoustic attenuation value.

Contrary to this prejudice, the invention proposes adapting transduceroperating frequency not only to the type of target organ but also to thespecific patient concerned. Advantageously, this measurement can be madeprior to each treatment, thereby allowing the optimum frequency of theHIFU apparatus to be adjusted, for example using formula (1) above.

Various solutions are possible for measuring acoustic attenuation.Measurement is advantageously performed by attenuation measurement inthe reflection mode. Ophir made an inventory of biological tissueattenuation measurement techniques using reflection (J. Ophir, T. H.Shawker, N. F. Maklad, J. G. Miller, Stephen W. Flax, P. A. Narayana andJ. P. Jones, “Attenuation estimation in reflection: progress andprospects”, Ultrasonic Imaging 6, pp 349-395, 1984). Generally speaking,two types of method for measuring attenuation in biological tissue canbe distinguished: frequency methods and time methods. The time methodsare better adapted to real time whereas the frequency methods providefiner measurement and are flexible, but require a larger computingoverhead.

Frequency methods are principally of two types: spectral differentialmethods where the information is contained in the variation of amplitudeof various spectral components, and spectral shift methods where theinformation is contained in signal central frequency shift.

Time (temporal) methods can also be divided into two categories.Firstly, they comprise methods employing the echographic signalamplitude which are the wideband or narrow band amplitude attenuationestimation methods. Secondly, they comprise time methods givinginformation on how the central frequency of a signal is changing (zerocrossing density methods). These various methods can be employed forcarrying out the invention.

Once the measurement has been performed, using, for example, one or theother of these methods, the optimum frequency for HIFU treatment isdeduced from the measurement results. A determination of this frequencycan advantageously be performed by applying equation (1) above. Applyingthis formula makes it possible to calculate optimum frequency for agiven amount of energy to be applied to the target; for this, all thatis needed is to reverse formula (1) to obtain the frequency value as afunction of attenuation.

The invention can readily be carried out in the apparatus describedbelow with reference to FIG. 1 et seq.

In another embodiment, in HIFU apparatus, the frequency of theultrasound employed is varied as a function of target tissuetemperature. The invention now provides a solution to the new problem ofvariation in attenuation as a function of target temperature. In effect,the attenuation factor varies with temperature in particular when thisexceeds 50° C. As variation for tissue subjected to thermal treatmentcan be twice its value at 37° C., the invention allows better use of theenergy, and application of treatment to a more precise region.

Contrary to all apparatus of the prior art, in which this variation isnot taken into consideration or simply ignored, the invention proposesvarying frequency during the duration of a shot. As was the case above,the variation in frequency during a shot can be obtained by applyingformula (1). For this, for a determined target acoustic power, formula(1) is reversed and the optimum frequency as a function of the targettemperature is found. Target temperature can be measured by MRI duringtreatment; it could also be calculated using the so-called bioheatequation which describes changes of heat during a shot. This equation isgiven in the publications covering tissue hyperthermia such as forexample in Bowman HF “The bioheat transfer equation and discriminationof thermally significant vessels” ann. New York Acad. of Sci. No. 335 pp155-160, 1981. The bioheat equation also makes it possible to calculatethe thermal dose needed for tissue necrosis as explained, for example,in Sapareto S A and Dewey W C “Thermal dose determination in cancertherapy” Int. J. Radiation Oncology Biol. Phys. N°10 pp 787-800, 1984.

The invention makes it possible to optimize heat delivery around thefocus, increase the speed with which elementary lesions are formedthereby decreasing the duration of treatment.

This variation in frequency during treatment can be employedindependently of, or in combination with, frequency variation prior totreatment. The invention that has just been described can be implementedin an apparatus of the type described below with reference to FIG. 1 etseq.

The invention further proposes, in HIFU apparatus, to vary frequency asa function of the thickness of the tissue through which the energypasses. In practice, ultrasound treatment transducers are not in directcontact with the target or tissue and the ultrasound firstly passesthrough a coupling fluid. The latter is generally contained in a pocketthat is applied to the tissue. To reach targets at a greater or lesserdepth, the position of the transducer is adjusted along the acousticaxes. This means that the distance covered by the ultrasound in patienttissue can vary.

It is proposed, in order to optimise effectiveness, to adapt or varyultrasound emitting frequency as a function of the thickness of tissueactually passed through. This thickness can for example be calculated bysubtraction, knowing the focal length and measurement distance betweenthe transducer and the first tissue interface. The latter can forinstance be determined by the technique described in French patentapplication serial No. 9406539.

Formula (1) can now be applied for determining optimum frequency, for agiven power Q, as a function of the thickness of absorbent medium d. Forthis, it is sufficient to reverse formula (1) to obtain F as a functionof d. Assuming this, we can ignore losses in the coupling medium, whichis legitimate for water, generally employed as the coupling medium.

The invention ensures that a given transducer is effective both for deepshots as well as for surface shots. It avoids shots that are toopowerful and low depth burns.

Variation in frequency according to the invention can be performedbefore or during treatment. It can be combined with variation infrequency as a function of target attenuation, calculated beforeshooting. It can also be combined with frequency variation as a functionof target temperature. It can also be used alone. The invention justdescribed can be implemented in an apparatus of the type described belowwith reference to FIG. 1 et seq.

The invention further proposes a solution to the new problem of lesionprogression during firing. This is based on a new finding that, in HIFUapparatus, the biological lesion in tissue originates close to the focalpoint and progresses towards the transducer at depths which consequentlybecome smaller and smaller. This is the origin of a new problem in thatthe frequencies chosen for one given depth of shooting are notnecessarily the most suitable during shooting if the biological lesionis formed at variable depths. Thus, if frequency was chosen optimallyfor lesion creation at the focal point, it becomes less and lesssuitable as the lesion approaches the transducers. In practice, this isreflected by a loss of efficiency during shooting. For example, a fewmilliseconds are enough to form a 5-10 mm lesion at the focal point butseveral seconds are needed for it to develop over some 20 mm in front ofthe focal point. With firing durations exceeding several seconds, theeffects of spread of heat are not negligible and can give rise tolesions the extent of which is hard to control. In this case, it isappropriate to adapt operating frequency to the displacement of thelesion.

The invention consequently proposes adapting the frequency over time, asa function of lesion displacement and consequently of the depth thereof.The law governing collision displacement can be determined not onlyexperimentally but also by simulation from a mathematical model.Frequency can then be adapted using formula (1), taking account ofvariation, brought about by shifting of the lesion, in the thickness oftissue passed through. One can also simply use the typical frequencyvalues given in the various embodiments described below.

In one embodiment, the invention is adapted to the case of a fixed focallength transducer for which lesion formation is accompanied by change offrequency during the shot. The table below gives examples of values forlesion dimension depending on shot duration. These values were obtainedfrom experiments on animals.

base distance Duration of depth of from lesion length of shot/dimensionlesion P to surface d lesion (P − of lesion (mm) (mm) d) in mm   2 sec17 7 10 4.5 sec 18 0 18

The depth P of the lesion is the distance between the point on thelesion furthest from the surface—typically the surface of the patient'sskin, or, in the case of endocavital treatment, the inner surface of thecavity used for treatment—and this surface. The distance d is thedistance between the point on the lesion closest to the surface, and thesurface. These two distances are shown on FIG. 1.

After 2 seconds shooting, the base of the lesion was situated at a depthof 7 mm and was 10 mm long. Between 2 and 4.5 seconds shooting, thelesion extended to reach the surface. We note thus that lesion depthvaries during shooting and that the lesion progresses towards thesurface; the invention proposes making use of this surprising finding tomake an appropriate adjustment to frequency. One can for example employa low frequency at the beginning of firing to initiate a deep lesion andthen high frequencies at the end of shooting when the lesion is close tothe surface. The following firing sequence is for example proposed:

Time (s) 0-1 1-2 2-3 3-4 Frequency (MHz) 1.8 2.25 2.75 3

Stated in other terms, frequency is changed every second, with frequencyincreasing. This embodiment, in which the frequency is increased bysteps, is the most simple to implement; other ways of varying frequencyfor increasing frequency during firing can be envisaged.

Frequency values given in the table are optimum for an intensity of 1000to 2000 W/cm² at the focal point, a 40 mm diameter transducer of focallength 40 mm, such as the applicant's “Ablatherm” apparatus used forendorectal prostate cancer treatment. Frequency values can vary as afunction of the treatment being followed and as a function of thetransducer and the lesions. The invention consequently provides higherefficiency and better lesion control by ensuring that firing “tracks”lesion formation. The invention, in this embodiment, proposes adaptingfrequency to the extent of the lesion during treatment.

Just like the case above, the invention can be used in combination withfrequency variation as a function of attenuation in the tissue, oftissue temperature, or as a function of the thickness of the couplingmeans.

The invention also proposes varying the position of the lesion withrespect to the fixed focal length type transducer focal point bychanging frequency during firing, or between shots. In this embodiment,the invention resides on the finding that tissue attenuation increaseswith frequency. The energy reaching the focal point consequentlydecreases as frequency increases and lesion formation occurs ahead ofthe focal point when frequency increases. The invention proposesproceeding with successive shots at different frequencies.

The following table gives values for lesion position as a function offiring frequency. These values are from experiments carried out onanimals.

distance Firing between base frequency/ of lesion and length ofdimensions of lesion depth surface d lesion (p − lesions P (mm) (mm) d)in mm  1.8 MHz 23   2.7 20.3 2.25 MHz 21.8 1.3 20.4 2.75 MHz 18.5 0  18.5   3 MHz 20.4 0   20.4

The other treatment parameters are:

Duration of emission for each shot=4.5 s

Idle time following each shot=5 s;

In all cases, the transducer surface was cooled.

For the highest frequencies, lesions are effectively created at lowerdepth. Lesion length remains fairly constant so that they get formedclose to the tissue surface.

To come back to the example of applicant's “Ablatherm” apparatustransducer, the transducer can either be excited at the frequency of2.25 MHz when it is the heart of the prostate which is being aimed ator, advantageously, at 3 MHz when it is desired to reach the posteriorregion of the prostate, in particular the capsule of the gland. Theinvention makes it possible to consequently adapt, for a given focallength and consequently without moving the probe, the depth at whichtissue is treated, by simply varying frequency. Using electrical orelectronic means, the region treated can be shifted without havingrecourse to mechanical movement or electronic focusing.

As above, the invention can be used in combination with variation infrequency as a function of attenuation in tissue, tissue temperature oras a function of the thickness of the coupling means.

In all the embodiments described above, the change in frequency can bediscrete or continuous. FIG. 1 is a diagrammatical view of HIFUapparatus for carrying out the invention. Apparatus 1 comprises meansfor emitting high intensity focused ultrasound, for example a cup 2 ofcomposite transducers, or a transducer array. The emitting means arewideband emitting means which focus the ultrasound onto a focal point,and are adapted to emit ultrasound over a range of frequencies having awidth of 40% of the central frequency, preferably a width of 50% of thecentral frequency; values of 2 to 3 MHz for bandwidth are suitable. Aband of frequencies of such a width, covering the frequency values givenabove, is suitable. Such a band of frequencies can be obtained forpiezo-composite-type transducers, i.e. transducers composed of aflexible matrix and ceramic transducers, coupling of which isessentially obtained by compressing the flexible matrix; in other words,energy coupling takes place principally not directly from the ceramicsbut rather via the matrix.

In these embodiments, frequency variations have an effect on thefocusing: a higher frequency produces a finer focal spot throughdiffraction phenomena and, consequently, higher intensity at the focalpoint for a given emitting power.

The emitting means 1 send ultrasound towards coupling medium 3, forexample degassed water, contained in an ultrasound-transparent casing 4.

The apparatus of FIG. 1 further comprises means 5 for measuring acousticattenuation around the focal point 9 of the emitting means; these means5 supply the results of measurements to the means 6 for adjusting thefocused ultrasound frequency. For acoustic attenuation variationmeasurement, the solution described in applicant's co-pending Frenchpatent application entitled “Method for measuring the effect oftreatment on tissue” can notably be employed. This particularlyadvantageous solution can be used instead of attenuation measurement bya conventional method. As this solution involves measurement before andafter shooting, it is advantageously implemented right from the secondshot; it has the advantage of being able to be implemented in real timeduring treatment.

The adjustment means perform focused ultrasound frequency adjustment,for example using equation (1), if needs be with the frequencycorrection mentioned above. Adjustment can advantageously be done beforeeach shot.

The apparatus of FIG. 1 additionally comprises means 8 for measuring thethickness of tissue passed through, for example for measuring thedistance between a fixed point and the casing 4 in contact with thetissue. Knowing the focal length, the means 8 can determine thethickness of tissue passed through. The measurement means can forexample employ mode-A echography, as described in French patentapplication serial number 94.06539. In that application, the transduceris a transducer array the central pad of which is employed forgenerating acoustic signals allowing attenuation to be measured byA-mode echography.

The results of calculation or measurement are supplied to the adjustingmeans 6 for focused ultrasound frequency. The means 6 perform frequencyadjustment as a function of tissue thickness passed through.

Advantageously, the means 6 are adjustable in different modes, as afunction of the type of treatment desired. In a first mode, theadjustment means adjust frequency as a function of attenuation at thetarget. In a second mode, the adjustment means adjust frequency as afunction of the thickness of tissue passed through. In a thirdadjustment mode, the adjustment means adjust frequency as a function ofattenuation at the target and thickness of tissue passed through. In afourth adjustment mode, the adjustment means adjust frequency as afunction of the distance between the base of the lesion and the surface.These adjustment modes make it possible to adjust frequency before eachshot, or before a series of shots.

Each of these adjustment modes can be associated with an adjustment modefor frequency during firing; in a fourth adjustment mode, the adjustmentmeans adjust frequency during firing as a function of the lesiontemperature; in a fifth adjustment mode, the adjustment means adjustfrequency during firing as a function of tissue thickness passed throughduring firing, taking account of displacement of the lesion duringfiring. In a sixth adjustment mode, the adjustment means adjustfrequency during firing as a function of lesion temperature and thethickness of tissue passed through during a shot, taking account ofdisplacement of the lesion during the shot. These latter threeadjustment modes can be combined with the first three modes.

FIG. 2 is a flow chart of one possible method for adjusting frequencyaccording to the invention. FIG. 2 shows the example of prostatetreatment, using HIFU apparatus with a variable-thickness couplingmedium.

At step 20, the apparatus is put into place, and the casing of thecoupling medium is put in contact with the patient's body. The focalpoint of the emitting device is brought close to the target to betreated, by a method known per se, for example by imaging the regionsurrounding the target, and viewing the focal point on the imagingdevice screen.

At step 22, the thickness d of the tissue passed through is measuredusing measuring means 8, knowing the focal length of the transducer.

At step 24, the acoustic attenuation μp of the patient's prostate ismeasured using the means 5 for measuring attenuation.

Knowing d and μp, the optimum firing frequency F1 is calculated at step26 for supplying a given energy to the target.

At step 28, knowing the law governing temperature change and the law fordisplacement of the lesion, the duration t1 of firing is calculatedbefore changing frequency. This calculation, as explained above, is doneusing the “bioheat” equation; one can also use the experimental valuesmentioned above.

At step 30, one can then calculate, for the position of the lesion aftera period of time t1, and for the temperature after the period of timet1, a new optimum frequency F2, using the new thickness of the tissuepassed through and the new attenuation which is a function of thetemperature reached.

Steps 28 and 30 are recommended until reaching a duration correspondingto a treatment of the whole of the target.

One can then proceed with the treatment.

Treatment can also be carried out at the same time as calculation offrequency Fi and the time ti for the next firing sequence. Thisembodiment is advantageous if the new attenuation is being measuredcontinuously or between each shot.

In the description above we have used the word “shot” for delivery ofultrasound at a given frequency; treatment can advantageously comprise avariety of such shots, separated or not separated by intervals duringwhich focused ultrasound is not emitted.

The adjustment of frequency according to the invention is carried out,preferably automatically, as a function of the selected treatment power.The method applies to all treatment powers, and does not provide anysuggestion regarding treatment power or total energy to be applied for agiven target. In this sense, frequency adjustment according to theinvention is only a technical method aimed at resolving the technicalproblem of optimum distribution of energy in the target, and solelywithin the target. Adjustment according to the invention is consequentlyindependent of the surgeon practising his art, though the choice oforgans to be treated, powers to be applied, duration of treatment orother parameters. Indeed, this adjustment of frequency has no functionor relation with the therapeutic effect of the treatment, which isdetermined by the surgeon performing the treatment.

Throughout the present description, the term “attenuation” has beenused. The term absorption could also be used; strictly speaking,absorption only takes into account spreading of heat and other losses inthe medium. On the contrary, attenuation is generally calculated fromoverall weakening of a signal. In practice, the ratio betweenattenuation and absorption is generally constant for a given tissue.

This invention is obviously not limited to the examples and embodimentsdescribed and illustrated, but may be subject to numerous variationsaccessible to those skilled in the art. It is clear that although theinvention was described with reference to the example of the prostate,it is not limited to such an organ, and can apply to other tissue. Theinvention could thus be used for hyperthermia treatment of the breast,liver, or other organs or tissue. It is also clear that the invention isnot limited to the embodiment shown in FIG. 1, and can be applied toendocavital apparatus such as the one disclosed in internationalapplication PCT/FR 94/00936.

What is claimed is:
 1. A method for treating a biological target by emitting high-intensity focused ultrasound toward a focal point, the method comprising the steps of: providing an ultrasound apparatus having a wideband ultrasound transducer for emitting the ultrasound; exciting the ultrasound transducer with a narrow band input signal so that the ultrasound transducer emits focused ultrasound energy in a narrow frequency range, said excitation occurring for a predetermined shot duration; measuring an attenuation factor of the ultrasound energy transmitted from the ultrasound transducer to the biological target; calculating an optimum frequency of the input signal supplied to the ultrasound transducer based on the measured attenuation so as to maximize an amount of energy absorbed by the biological target; and adjusting the input frequency of the signal supplied to the transducer based on the calculated optimum frequency.
 2. The method according to claim 1,wherein the attenuation of the ultrasound energy returned by the biological target is measured using a reflection method.
 3. The method according to claim 1 wherein the attenuation of the ultrasound energy returned by the biological target is measured using a frequency method.
 4. The method according to claim 1 wherein the attenuation of the ultrasound energy returned by the biological target is measured by determining variations in an amplitude of frequency components of the ultrasound energy.
 5. The method according to claim 1 wherein the attenuation of the ultrasound energy returned by the biological target is measured by determining a shift in a central frequency of the ultrasound energy.
 6. The method according to claim 1 wherein the optimum frequency of the signals supplied to the ultrasound transducer is calculated according to the formula: Q=2αFI ₀ Ge ^(−2αFd) where Q is an acoustic power absorbed per unit of volume α is the acoustic attenuation factor (Neper/cm/MHz) I₀ is an acoustic intensity at a transducer emission surface (W/cm²) G is an antenna gain F is the input frequency (MHz) d is the thickness of the absorbing medium (cm) wherein the measured attenuation factor, α, is substituted into said formula and the optimum input frequency, F, is calculated to yield a maximum value of the acoustic power absorbed, Q.
 7. The method according to claim 1 wherein the optimum frequency of the signals supplied to the ultrasound transducer is calculated before the shot duration.
 8. The method according to claim 1 wherein the optimum frequency of the signals supplied to the ultrasound transducer is calculated during the shot duration.
 9. A method for treating a biological target by emitting high-intensity focused ultrasound toward a focal point, the method comprising the steps of: providing an ultrasound apparatus having an ultrasound transducer for emitting the ultrasound; exciting the ultrasound transducer with an input signal so that the ultrasound transducer emits focused ultrasound energy in a narrow frequency range, said excitation occurring for a predetermined shot duration; measuring an attenuation factor of the ultrasound energy transmitted from the ultrasound transducer to the biological target; calculating an optimum frequency of an input signal supplied to the ultrasound transducer based on the measured attenuation so as to maximize an amount of energy absorbed by the biological target; and adjusting the input frequency of signals supplied to the transducer based on the calculated optimum frequency.
 10. A method for treating a biological target by emitting high-intensity focused ultrasound toward a focal point, the method comprising the steps of: providing an ultrasound apparatus having a wideband ultrasound transducer for emitting the ultrasound; exciting the ultrasound transducer with a narrow band input signal so that the ultrasound transducer emits focused ultrasound energy in a narrow frequency range, said excitation occurring for a predetermined shot duration; measuring attenuation of the ultrasound energy transmitted from the ultrasound transducer to the biological target; calculating an optimum frequency of an input signal supplied to the ultrasound transducer based on the measured attenuation so as to maximize an amount of energy absorbed by the biological target; and modifying the input frequency of signals supplied to the transducer based on the calculated optimum frequency.
 11. An apparatus for treating a biological target within a human body, the apparatus comprising: an wideband ultrasound transducer configured to emit high-intensity focused ultrasound toward a focal point; a coupler disposed between the ultrasound transducer and the human body to facilitate efficient transmission of the ultrasound to the biological target; the ultrasound transducer supplied with a narrow band input frequency signal to cause the ultrasound transducer to emit focused ultrasound energy in a narrow frequency range, said emission of ultrasound occurring for a predetermined shot duration; means for measuring an attenuation of the ultrasound energy transmitted from the ultrasound transducer to the biological target; and wherein an optimum frequency of an input signal supplied to the ultrasound transducer is calculated based on the measured attenuation so as to maximize an amount of energy absorbed by the biological target, and wherein the input frequency of signal supplied to the transducer is adjusted based on the calculated optimum frequency.
 12. A method for treating a biological target by emitting high-intensity focused ultrasound toward a focal point, said high-intensity focused ultrasound creating a lesion, the method comprising the steps of: providing an ultrasound apparatus having a fixed focus ultrasound transducer for emitting the ultrasound; exciting the ultrasound transducer with a narrow band input signal, said excitation occurring for a predetermined shot duration; and increasing an input frequency the signal supplied to the transducer during the shot duration to effectively treat the biological target—between.
 13. The method according to claim 12 wherein the frequency is varied continuously during the shot duration.
 14. The method according to claim 12 wherein the frequency is varied continuously during a portion of the shot duration.
 15. The method according to claim 12 wherein the frequency is varied according to a plurality of increasing frequency steps during the shot duration.
 16. The method according to claim 12 wherein the frequency is varied according to a plurality of increasing frequency steps during a portion of the shot duration.
 17. The method according to claim 12 wherein the frequency is varied according to a plurality of increasing non-linear frequency steps during the shot duration. 